The experimentation proposed here is designed to provide information to explain how extracellular changes or environmental changes affect the differentiation process. We propose that it is the external environment in which the cell finds itself which is deterministic in terms of muscle or cartilage development from embryonic chick limb mesenchymal cells. The information concerning composition of the environment is communicated through two systems: the NAD system and the system involved with the synthesis of cyclic AMP. With pool changes of NAD or cyclic AMP, chromosomal events are involved in the differentiation of the specific phenotype. There are sensing systems associated with chromatin which are capable of translating pool sizes of NAD or cyclic AMP into modification of chromosomal protein. Such modified chromosomal proteins may affect either differential transcription, replication or the accessiblity of other modifier proteins. The experimentation proposed here is designed to quantitate the internal changes of NAD and cyclic AMP and to correlate these with developmental events. Also proposed is the characterization of alterations of chromosomal proteins which are related to the differentiation and developmental events. Special emphasis is placed on identifying chromosomal proteins which are associated with either the NAD or cAMP systems as well as attempts to ascertain if these systems are functionally interfaced.